Tissue-specific inflammation induces cell state plasticity with oncogenic addiction in mucosal melanoma - PubMed
4 hours ago
- #HER2/3 inhibition
- #inflammation
- #mucosal melanoma
- Mucosal melanoma (MM) is an aggressive subtype resistant to therapies effective in cutaneous melanoma.
- Integrative analysis shows mucosa-specific inflammation enriches low-pigmented neural crest-like cancer cells, mediated by COX2+ macrophages and their secretome.
- Maintenance of this inflammation-induced neural crest-like state depends on HER2 and HER3 activation.
- Inhibition of HER2/3 with pan-HER inhibitors blocks cell state plasticity and overcomes chemoresistance in MM cell lines and PDX models.
- Findings highlight how tissue-specific inflammation drives melanoma stemness and chemoresistance, identifying potential treatments for MM.